UOC PATHOLOGICAL ANATOMY
Head: Edoardo Pescarmona, MD
We have shown that paracrine signaling from breast cancer cells causes activation of ID4 expression in tumor-associated macrophages. We have studied the prognostic relevance of coagulation activation in risk assessment and stratification in locally advanced breast cancer. We have demonstrated that pyrvinium pamoate induces death of triple-negative breast cancer stem-like cells and reduces metastases; and that aberrant transcriptional and post-transcriptional regulation of SPAG5, a YAP-TAZ-TEAD downstream effector fuels breast cancer cell proliferation. Finally, we have published an observational study on p53 and Bcl2 immunohistochemical expression across molecular subtypes in a large series of early breast cancer patients with long-term follow-up, and we have observed the loss of HER2 and the decreased T-DM1 efficacy in HER2 positive advanced breast cancer treated with dual HER2 blockade.
We have performed by liquid biopsy a cross-sectional analysis of circulating tumor DNA in primary colorectal cancer at surgery and during the post-surgery follow-up, and also showed the presence of a distinctive microRNA (miRNA) signature in the blood of colorectal cancer patients. Further, we have investigated the relationships between TRF2 and VEGF-A and prognosis/survival in colorectal cancer patients, and shown that BRAF status modulates interleukin 8 expression through a CHOP-dependent mechanism in colorectal cancer. In addition, we have demonstrated a direct plasmonic detection of circulating RAS mutated DNA in colorectal cancer patients, and we have performed a multicohort and cross-platform validation of a prognostic Wnt signature in colorectal cancer.
Gynecological & Urological tumours
In cervical carcinoma we have performed a study on the interlaboratory concordance of p16/Ki67 dual-staining interpretation in HPV-positive women in a screening population, we have evaluated the p16/Ki67 and E6/E7 mRNA accuracy and prognostic value in triaging HPV DNA positive patients, and we have assessed the p16/Ki67 adequacy and positivity in HPV-positive women from a screening population. Further, we have investigated the urinary expression of let-7c cluster as non-invasive tool to assess the risk of disease progression in patients with high grade non muscle invasive bladder cancer.
Head & Neck tumours
We have evaluated the Anyplex II HPV28 assay in the detection of human papillomavirus in archival samples of oropharyngeal carcinomas, and we have demonstrated that abnormal cytology in oropharyngeal brushings and in oral rinses is not associated with HPV infection. Further, we have shown that PI3K inhibitors curtail MYC-dependent mutant p53 gain-of-function in head & neck squamous cell carcinoma, and that HPV sensitizes oropharyngeal squamous carcinoma cells to cisplatin-induced apoptosis by inhibiting autophagy through E7-mediated degradation of AMBRA1.
We have shown that CytoMatrix is a simple and reliable tool for the characterization of lung cancer stem cells from malignant pleural effusions. Further, we have demonstrated the presence of KEAP1-driven co-mutations in lung adenocarcinoma unresponsive to immunotherapy despite high tumor mutational burden.
Soft tissues & bone sarcomas
We have proposed Next Generation Sequencing approaches for the identification of pathognomonic fusion transcripts in sarcomas, and we have evaluated the diagnostic and clinical impact of 18F-FDG PET/CT in staging and restaging soft-tissues sarcomas of the extremities and trunk. Further, we have published a retrospective analysis on the real-life journey of elderly patients in soft tissues and bone sarcomas.